Impact of Deep Neuromuscular Blockade During Total Hip Replacement Surgery on Postoperative Recovery and Immune Function (HIPPO)

Deep Versus Moderate Neuromuscular Blockade During Total HIP Replacement Surgery to Improve POstoperative Quality of Recovery and Immune Function: a Randomized Controlled Study

Monocenter randomized controlled trial to compare the effect of deep neuromuscular blockade (NMB) versus moderate NMB during total hip replacement surgery on postoperative quality of recovery and innate immune function.

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Postoperative Complications; Neuromuscular Blockade; Innate Inflammatory Response
• Intervention / Treatment: Drug: Rocuronium Bromide; Drug: Rocuronium Bromide

Detailed Description

Rationale: Neuromuscular blockade agents (NMB) may enable surgeons to optimize exposure during hip surgery. With an increasing depth of NMB, manipulation of muscles and adjunctive tissues may be easier, therefore reducing damage to muscles and adjunct tissues. Accumulating evidence exists that the use of deep NMB in laparoscopic surgery is associated with a better quality of recovery and lower pain scores. However, whether this accounts for open surgery is still unknown.

In addition, surgery is associated with postoperative immune suppression. Surgical stress and damage cause the release of Danger Associated Molecular Patterns (DAMPs). After trauma and sepsis, the release of DAMPs is associated with immune paralysis and a higher susceptibility to infectious complications. Previous research indicates that DAMPS are the origin of postoperative immune suppression. The use of deep NMB in hip surgery may reduce surgical damage and thereby lead to a better quality of recovery and secondarily a better preservation of immune cell function.

Primary objective: To establish the relationship between the use of deep neuromuscular blockade (NMB) versus moderate NMB and the quality of recovery after total hip replacement surgery (THR) Secondary objective: To establish the relationship between the use of deep NMB versus moderate NMB and innate immune function after THR surgery

Study design: A monocenter, blinded, randomized controlled clinical trial

Study population: adults who are scheduled for primary or secondary hip replacement surgery under general anaesthesia.

Intervention: Patients will be randomized between a deep NMB (post tetanic count (PTC) 1-2) and moderate NMB (Train-of-four (TOF) 1-2)

Primary endpoint: Quality of Recovery score (QoR-40) at postoperative day 1.

Secondary endpoints: postoperative innate immune function, QoR-40 at postoperative day 30, 30-day postoperative (infectious) complications, postoperative pain scores and opioid consumption

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • Recruiting
    • Radboudumc
    • Contact: Veerle Bijkerk, MD; Phone Number: 0031 24 361 5333
    • Principal Investigator: Michiel C Warlé, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of 18 years or older
• Scheduled for total hip replacement surgery under general anaesthesia
• Informed consent obtained

Exclusion Criteria:

• Insufficient control of the Dutch language to read the patient information and to fill out de questionnaires
• Known or suspected hypersensitivity to rocuronium or sugammadex
• Deficiency of vitamin K dependent clotting factors or coagulopathy
• Severe renal disease (creatinine clearance <30 ml/min), including patients on dialysis
• Severe liver disease (Child-Pugh Classification C)
• Known or suspected neuromuscular disorders impairing neuromuscular function
• Women who are or may be pregnant or currently breastfeeding
• Chronic use of psychotropic drugs
• Use of immunomodulatory medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deep neuromuscular blockade; Participant will receive deep neuromuscular blockade (PTC 1-2)	Drug: Rocuronium Bromide; Moderate NMB (TOF 1-2); Other Names: Bridion; Drug: Rocuronium Bromide; Deep NMB (PTC 1-2); Other Names: Bridion
Active Comparator: Moderate neuromuscular blockade; Participant will receive moderate neuromuscular blockade (TOF 1-2)	Drug: Rocuronium Bromide; Moderate NMB (TOF 1-2); Other Names: Bridion; Drug: Rocuronium Bromide; Deep NMB (PTC 1-2); Other Names: Bridion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery 40 (QoR-40) questionnaire score	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)	Postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery 40 (QoR-40) questionnaire score	40 points (minimum: extremely poor quality of recovery) to 200 points (maximum: excellent quality of recovery)	Postoperative day 30
Immune function represented by serum cytokine	Serum cytokine IL-6 level	Postoperative day 1
Immune function represented by IL-10	Serum cytokine IL-10 level	Postoperative day 1
Immune function represented by TNF-a	Serum cytokine TNF-a level	Postoperative day 1
Immune function represented by ex-vivo IL-6 production capacity	Ex-vivo IL-6 production capacity upon whole blood Lipopolysaccharide(LPS) stimulation	Postoperative day 1
Immune function represented by ex-vivo IL-10 production capacity	Ex-vivo IL-10 production capacity upon whole blood LPS stimulation	Postoperative day 1
Pain score by numeric pain rating (NRS) scale	pain scores with NRS 0 (no pain) to 10 (severe pain)	During hospital admission up to 3 days postoperative
Postoperative complications	postoperative complications scored by Clavien-Dindo classification; grade 0 (no deviation from ideal) grade 5 (death of patient)	30 postoperative days
Infectious postoperative complications	Postoperative infectious complications scored the definitions of the StEP-COMPAC group initiative	30 postoperative days
Analgesia consumption	non-cumulative and cumulative opioid use per day in morphine equivalent	During hospital admission up to 3 days postoperative

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Postoperative Complications; Physiological Effects of Drugs; Peripheral Nervous System Agents; Anticonvulsants; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Bromides; Rocuronium
• Other Study ID Numbers: NL81931.091.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be analyzed for publication. After that it belongs to Radboud umc where other researchers of Radboud umc may or may not include this database to their study. But there will be no active sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No